Endocrine Disruptors in Food, Estrobolome and Breast Cancer.

The microbiota is now recognized as one of the major players in human health and diseases, including cancer. Regarding breast cancer (BC), a clear link between microbiota and oncogenesis still needs to be confirmed. Yet, part of the bacterial gene mass inside the gut, constituting the so called "estrobolome", influences sexual hormonal balance and, since the increased exposure to estrogens is associated with an increased risk, may impact on the onset, progression, and treatment of hormonal dependent cancers (which account for more than 70% of all BCs). The hormonal dependent BCs are also affected by environmental and dietary endocrine disruptors and phytoestrogens which interact with microbiota in a bidirectional way: on the one side disruptors can alter the composition and functions of the estrobolome, ad on the other the gut microbiota influences the metabolism of endocrine active food components. This review highlights the current evidence about the complex interplay between endocrine disruptors, phytoestrogens, microbiome, and BC, within the frames of a new "oncobiotic" perspective.

Screening for Physical Activity Levels in Non-Metastatic Breast Cancer Patients Undergoing Surgery: An Observational Study.

BACKGROUND: Physical activity (PA) can play a role in lowering the risk of breast cancer (BC), but also in reducing perioperative complications and treatments related side effects, improving the quality of life and decreasing mortality in BC survivors. PA and nutritional screening are not offered to patients after cancer diagnosis as standard of care, even in high quality breast units. METHODS: From February 2019 to March 2020, we performed a preoperative physical and nutritional screening in 504 consecutive BC patients waiting for surgery. The screening included an IPAQ questionnaire to evaluate the level of physical activity; nutritional screening with measurement of anthropometric parameters (weight, height, waist and hips circumference, BMI, and waist hip ratio) and evaluation of body composition using Bioelectrical Impedance Analysis (BIA). RESULTS: The majority of patients in our series resulted physically inactive: clustering the IPAQ scores, 47% of patients proved to be physically inactive (MET score <700), 34% moderately active (MET score 700-2520), and only 19% physically active (MET score > 2520). In addition, approximately half of the patients (49.01%) resulted overweight or obese, and more than half (55.2%) had a percentage of fatty tissue over the recommended cut off for adult women. CONCLUSIONS: Our data confirm that assessment of PA levels should become part of the standard preoperative evaluation of BC patients and behavioral interventions should be offered to them, in order to pre-habilitate for surgery and improve outcomes. IPAQ Questionnaire and body composition analysis could be quick and easy screening tools in order to identify which patients may need more support in being active during and after anticancer treatments.

A Model of an Integrative Approach to Breast Cancer Patients.

BACKGROUND: Breast cancer (BC) survivors have physical and psychological needs that require convincing responses by health care providers. The quality of life issue and clinical unmet needs are among the main reasons pushing a number of patients toward "natural" therapies that are often misleading and alternative to mainstream cancer care. Integrative Oncology (IO) tries to respond to many of those needs, by combining lifestyle counseling, body-mind activities, and complementary evidence-informed therapies with anticancer standard treatments. METHODS: In our model at Fondazione Policlinico Gemelli (FPG), every woman diagnosed with a BC waiting for surgery or candidate to neoadjuvant chemotherapy undergoes a preliminary psycho-oncological distress evaluation and a brief lifestyle interview. Anthropometric measurements, body composition analysis, and individual levels of physical activity are recorded. Patients are given evidence based recommendations about the advisable diet and physical activity in a prehabilitation setting. A physician provides patients with information about integrative care plans to treat symptoms related to the disease or its treatments. Therapeutic approaches include acupuncture, mindfulness-based protocols, qigong, massage therapy, and classes of music/art therapy. RESULTS: Between September 2018 and February 2020, the Center for Integrative Oncology at FPG has carried out 1249 lifestyle counseling sessions, 1780 acupuncture treatments, 1340 physiotherapy sessions, 3261 psycho-oncological consultations, 218 herbal medicine counseling sessions. Moreover, 90 BC patients completed the mindfulness based stress reduction (MBSR) protocol and 970 patients participated in qigong, art therapy, and music therapy classes. CONCLUSIONS: Our integrative approach aims to achieve a person-centered medicine by improving symptoms management, adherence to oncological protocols, and eventually overall quality of life.

Lifestyle Characteristics in Women Carriers of BRCA Mutations: Results From an Italian Trial Cohort.

BACKGROUND: Women with deleterious mutations in BRCA1/2 have a high lifetime penetrance of developing breast cancer and/or ovarian cancer. Genetic and/or environmental factors may influence BRCA penetrance, and identifying modifiable exposures might be valuable for prevention. PATIENTS AND METHODS: We implemented a multicenter prospective 2-arm (1:1) randomized controlled trial to investigate whether a Mediterranean dietary intervention with moderate protein restriction would reduce potential modulators of BRCA penetrance such as insulin-like growth factor 1 (IGF-1), body weight, and metabolic risk factors. We studied the baseline characteristics of women with BRCA-positive disease who joined the trial cohort, focusing on the relationships between selected lifestyle exposures, metabolic/anthropometric parameters, and BRCA-related cancer. RESULTS: A total of 502 women (304 with a previous diagnosis of breast cancer and/or ovarian cancer and 198 unaffected) with deleterious BRCA mutations, with or without a previous cancer, aged 18 to 70 years and without metastases were included. Late age at menarche and pregnancy were negatively associated with BRCA-related cancer, especially in women with BRCA1-positive disease. Higher fat mass and the presence of 4 or 5 metabolic risk factors were significantly associated with BRCA-related cancer (hazard ratio, 1.87, 95% confidence interval, 1.21-2.88; and hazard ratio, 1.87, 95% confidence interval, 1.11-3.19, respectively), with greater effect in BRCA2-positive women. CONCLUSIONS: Our findings confirm previous observations about reproductive factors in women with BRCA disease and suggest a potential impact of metabolic factors in BRCA-related cancer. The prospective follow-up of the trial cohort will enable us to study the environmental modulators of BRCA penetrance and their impact in relation to the history of BRCA-related cancer. [ClinicalTrials.gov NCT03066856].

A Mediterranean Dietary Intervention in Female Carriers of BRCA Mutations: Results from an Italian Prospective Randomized Controlled Trial.

Background: Women carriers of BRCA1/2 mutations face a high lifetime risk (penetrance) of developing breast and/or ovarian cancer. Insulin-like growth factor I (IGF-I), body weight and markers of insulin resistance affect BRCA penetrance. We conducted a multicenter prospective two-armed (1:1) randomized controlled trial (NCT03066856) to investigate whether a Mediterranean dietary intervention with moderate protein restriction reduces IGF-I and other metabolic modulators of BRCA penetrance. Methods: BRCA carriers, with or without a previous cancer, aged 18-70 years and without metastases were randomly assigned to an active dietary intervention group (IG) or to a control group (CG). The primary endpoint of the intervention was the IGF-I reduction. Results: 416 women (216 in the IG and 200 in the CG) concluded the six-month dietary intervention. The IG showed significantly lowered serum levels of IGF-I (-11.3 ng/mL versus -1.3 ng/mL, p = 0.02), weight (-1.5 Kg versus -0.5 Kg, p < 0.001), waist circumference (-2 cm versus -0.7 cm, p = 0.01), hip circumference (-1.6 cm versus -0.5 cm, p = 0.01), total cholesterol (-10.2 mg/dL versus -3.6 mg/dL, p = 0.04) and triglycerides (-8.7 mg/dL versus + 5.5 mg/dL, p = 0.01) with respect to the CG. Conclusions: A Mediterranean dietary intervention with moderate protein restriction is effective in reducing IGF-I and other potential modulators of BRCA penetrance.

Characterization of human breast tissue microbiota from core needle biopsies through the analysis of multi hypervariable 16S-rRNA gene regions.

Breast microbiota compositions are not well understood, and a few recent reports have begun to explore the correlation between breast tissue dysbiosis and cancer. Given that various methods for breast microbiota detection were used, the aim of the present paper was to clarify which hypervariable region of the 16S-rRNA gene (V2, V3, V4, V6 + 7, V8, and V9) is the most informative for breast tissue microbiota. Core needle biopsies (CNBs) were compared with surgical excision biopsies (SEBs) to find a less invasive form of recovery useful for the analysis of a larger statistical population and potentially for diagnostic use of breast tissue microbiota. Finally, this study was the first to analyse the breast microbiota of tumours and paired normal tissues of a Mediterranean population. Our findings showed that the V3 region is the most informative for breast tissue microbiota, accounting for 45% of all reads. No significant differences were found between CNB and SEB specimens in terms of total reads and numbers of Operational Taxonomic Units (OTUs). Moreover, we find that more similarities than differences exist between tumours and adjacent normal tissues. Finally, the presence of the Ralstonia genus is associated with breast tissue.